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US3544585A - N'-(4-(hydroxymethyl)-5-pyrazolyl) amidines - Google Patents

N'-(4-(hydroxymethyl)-5-pyrazolyl) amidines Download PDF

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US3544585A
US3544585A US672717A US3544585DA US3544585A US 3544585 A US3544585 A US 3544585A US 672717 A US672717 A US 672717A US 3544585D A US3544585D A US 3544585DA US 3544585 A US3544585 A US 3544585A
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pyrazolyl
hydroxymethyl
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Leo Ralph Swett
James Daniel Ratajczyk
Patrick Richard Young
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Abbott Laboratories
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/38—Nitrogen atoms

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  • the reaction is carried out under heat and with an excess of the formylated secondary amine according to the Vilsmeier-Haack aldehyde synthesis reaction.
  • the catalyst generally employed in this reaction is phos- 3,544,585 Patented Dec. 1, 1970 phorous oxychloride since this agent is unusually suited to accomplish the condensation of the formyl group at the 4-position of the pyrazole ring.
  • An excess amount of formylated secondary amine must be used since it supplies the formyl group for the 4-position condensation as Well as supplying material for the condensation to the amine group at the 5-position on the pyrazole ring. That is, the formylated secondary amine supplies the carbon atom adjacent the double bond at the 5-position nitrogen atom.
  • the formylated secondary amines suitable in the practice of this invention include the following: l-formylpiperidine, 1-formyl-4-methylpiperazine, diethylformamide, l-formylmorpholine and dimethylformamide.
  • R is loweralkyl
  • other acylated amines may be used.
  • N,N-dimethylacetamide in the presence of phosphorous oxychloride condenses with the l,3-disubstituted-S-aminopyrazole to yield N'-(l,3-disub stituted-S-pyrazolyl)-N,N-dimethylacetamidine.
  • the 4-formyl group can then be introduced into the pyrazole nucleus by the use of dimethylformamide and phosphorous oxychloride.
  • EXAMPLE A Preparation of 5-amino-l,3-diphenylpyrazole To a stirred solution of 550 ml. of water and 150 ml. of concentrated hydrochloric acid, is added dropwise 108 grams (1.0 molar) of phenylhydrazine. Following this addition, 144 grams (1.0 molar) of 3-imino-3-phenylpropionitrile is added and the reaction mixture is then heated to 90 C. for 30 minutes. To the heated reaction mixture is slowly added ml. of concentrated hydrochloric acid and the mixture is heated to reflux for one hour. The mixture is then cooled in an ice bath and made alkaline by the addition of about 250 ml. of concentrated ammonium hydroxide until a precipitate forms.
  • the precipitate is filtered and Washed thoroughly with Water, then dried.
  • the product is crystallized from ethanol and water yielding 153 grams of 5-amino-1,3-diphenylpyrazole having a melting point of 13l-133 C.
  • Examples A and B illustrate methods for making the S-amino-l,3-disubstituted pyrazoles necessary as one of the starting materials to prepare the compounds of the instant invention, such methods are known in the art. Furthermore, the 5-amino-1,3-disubstituted pyrazoles are known compounds and are therefore not deemed to be a part of this invention, except to the extent that they are starting materials for making the novel compounds disclosed herein.
  • the l[N (4-formyl-1,3-diphenyl-5-pyrazolyl) -formimidoyl]piperidine is suspended in methanol and cooled in an ice bath with stirring. An equimolar proportion of sodium borohydride is added and the reaction mixture is allowed to come to room temperature and is stirred for 3 to 4 hours. A precipitate forms which is filtered off. Water is added to the filtrate until crystallization begins, and the precipitate is filtered and dried. Recrystallization from ethyl acetate yields 7.4 grams of l-[N-[4-(hydroxymethyl) 1,3 diphenyl 5-pyrazolyl]formimidoy11piperidine, having a melting point of 170-17l C.
  • the other members of this series of compounds may be similarly prepared. That is, the desired compound is obtained by reacting the appropriate S-amino-1,3-disubstituted pyrazole with the corresponding formylated secondary amine and phosphorous oxychloride, and reducing the product of this reaction with a suitable reducing agent such as sodium borohydride, lithium aluminum hydride, or other known reducing agents.
  • a suitable reducing agent such as sodium borohydride, lithium aluminum hydride, or other known reducing agents.
  • Table I following below lists several specific embodiments prepared in accordance with this procedure. Columns A and B describe the reactants, Column C, the product, and Column D, an identifying physical constant, e.g., melting point in degrees centigrade.
  • hal This material may then be used as starting material in accordance with the procedure of Example 1 to give the 4-formyl derivative which on reduction yields a halosubstituted phenyl moiety in the l-position of the pyrazole ring.
  • Examples of such compounds include N'[4-(hydroxymethyl) 1-(4-fluorophenyl)-3-phenyl-5pyrazolyl]- N,N dimethylformamidine; N [4 (hydroxymethyl) 1 (4 chlorophenyl) 3-phenyl 5 pyrazolyl] N,N-dimethyl formamidine; N [4 (hydroxymethyl) 1 (4- I TABLE I A B 0* D Example:
  • the compounds of this invention exhibit valuable pharmacological properties, especially as anti-inflammatory and anti-pyretic agents.
  • a group of rats are injected with Brewers yeast by intramuscular injection to produce a feverish condition.
  • the group is split into a control group and a test group.
  • the test compounds are administered to the test group and placebos to the control group.
  • Administration may be oral or by injection. Rectal temperatures are taken at hourly intervals after administration. The 3 hour reading is used to calculate fever and percent reduction in fever between drug and placebo groups.
  • Table II below shows the results from a representative borohydride yielding N [4 (hydroxymethyl) 1,3 dinumber of the compounds of the instant invention. In each case, administration is by the oral route. The doses indicated in the table are given in terms of milligrams per kilogram of body weight of the rat. The term LD represents the dosage at which the test compound is toxic to 50 percent of the animals in the test group.
  • Test compounds are administered to a group of test rats 30 minutes prior to an injection of carrageenan into the hind paw of the rats. Peak edema occurs 3 hours after the phlogistic injection, at which time the percent inhibition is calculated from the difference between the drug and placebo groups.
  • the control group is administered water or saline as the placebo. Administration may be by the oral route or by injection.
  • Table HI shows the results for a representative number of the compounds of this invention when tested according to this procedure.
  • the compounds are administered by the oral route.
  • the dosages are given in terms of milligrams of compound per kilogram of animal body weight.
  • the LD represents the dosage at which the test compound is toxic to 50 percent of the morpholine.
  • the compounds of this invention may be administered orally, or as injectable solutions.
  • Oral administration includes tablet preparations as well as oral suspensions and emulsions.
  • Administration by injection includes intramuscular, intraperitoneal as well as intravenous injections. Methods for formulating such preparations as tablets, emulsions, and injecta-ble solutions are generally known in the art.
  • R Y wherein X is selected from the group consisting of phenyl and loweralkyl; Y is selected from the group consisting of phenyl, loweralkyl and halophenyl; R is a member selected from the group consisting of hydrogen and loweralkyl; and R is a member selected from the group consisting of diloweralkylamino, piperidino, l-piperazinyl, 4-methyl-l-piperazinyl, and morpholino.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Catalysts (AREA)

Description

United States Patent ice 3,544,585 -[4-(HYDROXYMETHYL) -5-PYRAZOLYL] AMIDINES Leo Ralph Swett and James Daniel Ratajczyk, Waukegan,
and Patrick Richard Young, Winthrop Harbor, 11]., assignors to Abbott Laboratories, North Chicago, 111., a corporation of Illinois No Drawing. Filed Oct. 4, 1967, Ser. No. 672,717
Int. Cl. C07d 49/20 US. Cl. 260-310 2 Claims ABSTRACT OF THE DISCLOSURE A novel series of N'-[4-hydroxymethyl)-5-pyrazolyl] amidines which are useful as effective anti-inflammatory agents. These compounds are prepared by reacting 5- amino-l,3-disubstituted pyrazole with the appropriate formylated amine, and reducing the product obtained thereby to yield the desired compound.
DESCRIPTION OF INVENTION This invention is directed to a novel series of chemical compounds having the general structural formula:
I R Y wherein A and W each represent loweralkyl or, A and W together form a cyclic secondary amine, in the presence of a suitable catalyst. This reaction yields a pyrazole derivative having the amide condense at the 5-amino position and the formyl group substituted at the 4-position. This compound is then reduced with any suitable reducing agent to yield the final product.
This reaction scheme may be represented as follows:
The reaction is carried out under heat and with an excess of the formylated secondary amine according to the Vilsmeier-Haack aldehyde synthesis reaction. The catalyst generally employed in this reaction is phos- 3,544,585 Patented Dec. 1, 1970 phorous oxychloride since this agent is unusually suited to accomplish the condensation of the formyl group at the 4-position of the pyrazole ring. An excess amount of formylated secondary amine must be used since it supplies the formyl group for the 4-position condensation as Well as supplying material for the condensation to the amine group at the 5-position on the pyrazole ring. That is, the formylated secondary amine supplies the carbon atom adjacent the double bond at the 5-position nitrogen atom.
The formylated secondary amines suitable in the practice of this invention include the following: l-formylpiperidine, 1-formyl-4-methylpiperazine, diethylformamide, l-formylmorpholine and dimethylformamide. In the case Where R is loweralkyl, other acylated amines may be used. For example, N,N-dimethylacetamide in the presence of phosphorous oxychloride condenses with the l,3-disubstituted-S-aminopyrazole to yield N'-(l,3-disub stituted-S-pyrazolyl)-N,N-dimethylacetamidine.
The 4-formyl group can then be introduced into the pyrazole nucleus by the use of dimethylformamide and phosphorous oxychloride.
In order to better illustrate this invention, reference is made to the following examples which are intended to describe several embodiments of the invention, and are not intended to limit same thereby.
EXAMPLE A Preparation of 5-amino-l,3-diphenylpyrazole To a stirred solution of 550 ml. of water and 150 ml. of concentrated hydrochloric acid, is added dropwise 108 grams (1.0 molar) of phenylhydrazine. Following this addition, 144 grams (1.0 molar) of 3-imino-3-phenylpropionitrile is added and the reaction mixture is then heated to 90 C. for 30 minutes. To the heated reaction mixture is slowly added ml. of concentrated hydrochloric acid and the mixture is heated to reflux for one hour. The mixture is then cooled in an ice bath and made alkaline by the addition of about 250 ml. of concentrated ammonium hydroxide until a precipitate forms.
The precipitate is filtered and Washed thoroughly with Water, then dried. The product is crystallized from ethanol and water yielding 153 grams of 5-amino-1,3-diphenylpyrazole having a melting point of 13l-133 C.
EXAMPLE B Preparation of S-amino-l-methyl-3-phenylpyrazole A mixture of 13 grams (0.09 mole) of benzoylacetonitrile and 4.1 grams (0.09 mole) of methylhydrazine is refluxed together in 75 ml. of ethanol for 3 hours. The solvent is then removed in vacuo and the residual oil crystallized from ethyl acetate and a solvent consisting of a mixture of saturated hydrocarbons consisting mainly of hexane, having a boiling point of 6068 C. and commonly known by the trademark Skellysolve B, yielding 8.1 grams of S-amino-l-methyl-3-phenylpyrazole having a melting point of 124-l26' C.
Although Examples A and B illustrate methods for making the S-amino-l,3-disubstituted pyrazoles necessary as one of the starting materials to prepare the compounds of the instant invention, such methods are known in the art. Furthermore, the 5-amino-1,3-disubstituted pyrazoles are known compounds and are therefore not deemed to be a part of this invention, except to the extent that they are starting materials for making the novel compounds disclosed herein.
The following examples illustrate methods of preparing various members of the N'-[4-(hydroxymethy)-5- pyrazolyl]amidine series of this invention.
3 EXAMPLE 1 1- [N- [4- (hydroxymethyl) -1 3-diphenyl-5-pyrazolyl] formimidoyl] -piperidine A mixture of 23.5 grams (0.1 mole) of -amino-l,3- diphenylpyrazole and 45 grams (0.4 mole) of formylpiperidine is heated to 70 C. and to this mixture is added dropwise 63 grams (0.41 mole) of phosphorous oxychlo ride with stirring. After the addition is complete, the mixture is heated to 90 C. for one hour. The mixture is then poured onto ice and stirred until the complex is hydrolyzed. A saturated solution of sodium bicarbonate is added until the mixture is alkaline. The crude product is filtered, washed with water and crystallized from ethanol yielding 12.8 grams of 1-[N-(4-formyl-1,3-diphenyl 5 p-yrazolyl) formimidoyl1piperidine, having a melting point of 140l42. C.
The l[N (4-formyl-1,3-diphenyl-5-pyrazolyl) -formimidoyl]piperidine is suspended in methanol and cooled in an ice bath with stirring. An equimolar proportion of sodium borohydride is added and the reaction mixture is allowed to come to room temperature and is stirred for 3 to 4 hours. A precipitate forms which is filtered off. Water is added to the filtrate until crystallization begins, and the precipitate is filtered and dried. Recrystallization from ethyl acetate yields 7.4 grams of l-[N-[4-(hydroxymethyl) 1,3 diphenyl 5-pyrazolyl]formimidoy11piperidine, having a melting point of 170-17l C.
Following the procedure of Example 1, the other members of this series of compounds may be similarly prepared. That is, the desired compound is obtained by reacting the appropriate S-amino-1,3-disubstituted pyrazole with the corresponding formylated secondary amine and phosphorous oxychloride, and reducing the product of this reaction with a suitable reducing agent such as sodium borohydride, lithium aluminum hydride, or other known reducing agents. Table I following below lists several specific embodiments prepared in accordance with this procedure. Columns A and B describe the reactants, Column C, the product, and Column D, an identifying physical constant, e.g., melting point in degrees centigrade.
phenyl-S-pyrazolyl]-N,N-dimethylacetamidine, having a melting point of 140-142 C.
Following the procedure of Example A and by using the appropriately substituted halophenylhydrazine in place of phenylhydrazine, one may prepare the S-amino-l-halophenylpyrazoles according to the following reaction scheme:
@wz-omorr hell-@NHNH:
| hal This material may then be used as starting material in accordance with the procedure of Example 1 to give the 4-formyl derivative which on reduction yields a halosubstituted phenyl moiety in the l-position of the pyrazole ring. Examples of such compounds include N'[4-(hydroxymethyl) 1-(4-fluorophenyl)-3-phenyl-5pyrazolyl]- N,N dimethylformamidine; N [4 (hydroxymethyl) 1 (4 chlorophenyl) 3-phenyl 5 pyrazolyl] N,N-dimethyl formamidine; N [4 (hydroxymethyl) 1 (4- I TABLE I A B 0* D Example:
2 5-amino1,3-diphenylpyrazole 1-f0nnyl-4-methylpiperazine 1-[N-[4-(hydroxymethyl)-1,3-diphenyl5- 126-128 pyrazolyl]-formimidoy1]-4-methyl iperazine. 3 5-amino-1,3-dipheny1pyrazole Diethylformamide N,N-diethy1-N'-[4-(hydroxymethyl -1,3- 152-154 diphenyl-5-pyrazolyl]formamidine. 4 Eamino-lfi-diphenylpyramle 4-formylm0rpho1ine 4-[N-[4-(hydroxymethyl)-1,3-di henyl-5- 170-172 pyrazolyl]l'orm.imidoyl]morpholine. 5 5-amino-3-methyl-l-phenylpyrazole-... Dimethylformamide N-[4-(hydroxymethyD-3-methyl-l-phenyl-s- 118-120 pyrazolyl]-N,N-dimethylformamidjne. 6 5-amino-l-methyl-3-phenylpy'razOle.-.. Dimethylformamide N-[4-(hydroxymethyl)-1-methyl-3-pheny1-5- 132-133 pyrazolyl]N,N-dimethylformamidine. 7 5amino-1,3-diphenylpyraz0le Dimethylformamide N-[4(hydroxymethyl)-1,3-diphenyl-5- 149-151 V pyrazolyl]-N,N-dimethyliormamidine. 8 5-amino-1,3-dimethylpyraz01e Dimethylformamide N -[4-(hydroxymethyl)-1,3-dimethyl-5- 93-000 pyrazolyl]-N,N-dimethylformamidine. 9 s-amino-l-phenylpyrazole Dunethylt'onnamide N-[4-(hydroxymethyl)-1- heny1-5-pyrazoly11- Oil N,N-dimethylformamidine.
*The compounds shown in this column represent the final products obtained after reduction of the intermediate formed by the reaction of the starting materials listed in Columns A and B.
EXAMPLE 10 N-[4-(hydroxymethyl)-1,3-diphenyl-5-pyrazolyl] N,Ndimethylacetamidine Following the procedure of Example 1, 23.5 grams (0.1 mole) of S-amino-1,3-diphenylpyrazole is reacted with 35 grams (0.4 mole) of N,N-dimethylacetamide and phosphorous oxychloride. Crystallization from ethanol yields 16.8 grams of N-(1,3-diphenyl-5-pyrazolyl)-N,N- dimethylacetamidine. The compound is then reacted with dimethylformamide and phosphorous oxychloride, repeating the same reaction scheme yielding N'-(4-forn1yl- 1,3-diphenyl-5-pyrazolyl)-N,N-dimethylacetamidine. This intermediate is then reduced by reaction with sodium The compounds of this invention exhibit valuable pharmacological properties, especially as anti-inflammatory and anti-pyretic agents. In order to illustrate anti-pyretic properties, a group of rats are injected with Brewers yeast by intramuscular injection to produce a feverish condition. The group is split into a control group and a test group. When the fever has stabilized at 3 degrees F. or higher, the test compounds are administered to the test group and placebos to the control group. Administration may be oral or by injection. Rectal temperatures are taken at hourly intervals after administration. The 3 hour reading is used to calculate fever and percent reduction in fever between drug and placebo groups.
Table II below shows the results from a representative borohydride yielding N [4 (hydroxymethyl) 1,3 dinumber of the compounds of the instant invention. In each case, administration is by the oral route. The doses indicated in the table are given in terms of milligrams per kilogram of body weight of the rat. The term LD represents the dosage at which the test compound is toxic to 50 percent of the animals in the test group.
TABLE II Percent reduction Dose, mgJkg.
Compound mgJkg.
Number:
1 N-[4-(hydroxymethyl)- 1,3-diphenyl-5-pyrazo1y1]-N,N-dimethy1- formami e.
2 N-[4-(hydroxymethyl)- In order to demonstrate anti-inflammatory activity, a modification of the method described by C. A. Winter, et al., Proc. Soc. Exp. Med., 1962, 1112544 is utilized. Test compounds are administered to a group of test rats 30 minutes prior to an injection of carrageenan into the hind paw of the rats. Peak edema occurs 3 hours after the phlogistic injection, at which time the percent inhibition is calculated from the difference between the drug and placebo groups. The control group is administered water or saline as the placebo. Administration may be by the oral route or by injection.
Table HI below shows the results for a representative number of the compounds of this invention when tested according to this procedure. In each case, the compounds are administered by the oral route. The dosages are given in terms of milligrams of compound per kilogram of animal body weight. Again, the LD represents the dosage at which the test compound is toxic to 50 percent of the morpholine.
The compounds of this invention may be administered orally, or as injectable solutions. Oral administration includes tablet preparations as well as oral suspensions and emulsions. Administration by injection includes intramuscular, intraperitoneal as well as intravenous injections. Methods for formulating such preparations as tablets, emulsions, and injecta-ble solutions are generally known in the art.
We claim:
1. A chemical compound having the formula:
I R Y wherein X is selected from the group consisting of phenyl and loweralkyl; Y is selected from the group consisting of phenyl, loweralkyl and halophenyl; R is a member selected from the group consisting of hydrogen and loweralkyl; and R is a member selected from the group consisting of diloweralkylamino, piperidino, l-piperazinyl, 4-methyl-l-piperazinyl, and morpholino.
2. A compound according to claim 1 wherein X and Y are each phenyl, R is hydrogen and R is dimethylamino.
References Cited UNITED STATES PATENTS 2,858,309 10/1958 Druey et al. 260-310C 3,318,904 5/1967 Schmidt et al. 260268Het 3,404,143 10/1968 Hebky et al. 260-564 OTHER REFERENCES Arndt et al. I German Application 1,172,081, June 1964 (2 page spec.), 260-564.
Arndt et al. II German Application 1,220,195, June 1966 (3 page spec.), 260-564.
Finar et al. Jour. Chem. Soc. (London), 1959, pp. 1819-23, QD1.C6.
Hill et al. Jour. Amer. Chem. Soc., vol. 48, pp. 3214- 19 (1926), QD1.A5.
Musante et al. 62122. Chim. Ital, vol. 89, p. 1582 relied on (1959), QD1.G28.
Shriner et al. Chem. Rev., vol. 35, pp. 362, 365-7 and 373-4 relied on (1944), QD1.A563.
Wagner et al. Synthetic Organic Chemistry, pp. 635-6, N.Y., Wiley, 1953, QD262.W24.
NATALIE TROUSOF, Primary Examiner US. Cl. X.R.
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3941881A (en) * 1975-03-14 1976-03-02 American Cyanamid Company Novel 3 or 5-aminopyrazolium salts and fungicidal use thereof

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CZ301894B6 (en) * 2000-10-18 2010-07-21 Ciba Specialty Chemicals Holding Inc. Process for preparing bis-benzazolyl compounds
CN102070627A (en) * 2010-12-29 2011-05-25 河北星宇化工有限公司 Method for preparing 2,5-bis(5-tert-butyl-2-benzoxazolyl)thiophene

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2858309A (en) * 1956-05-07 1958-10-28 Ciba Pharm Prod Inc New aminobenzene sulfonamide
US3318904A (en) * 1962-08-17 1967-05-09 Ciba Geigy Corp Nitrothiazolyl amidines
US3404143A (en) * 1964-12-21 1968-10-01 Sofa Spojene Podniky Pro Zdrav Iodinated x-ray contrast agents

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2858309A (en) * 1956-05-07 1958-10-28 Ciba Pharm Prod Inc New aminobenzene sulfonamide
US3318904A (en) * 1962-08-17 1967-05-09 Ciba Geigy Corp Nitrothiazolyl amidines
US3404143A (en) * 1964-12-21 1968-10-01 Sofa Spojene Podniky Pro Zdrav Iodinated x-ray contrast agents

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3941881A (en) * 1975-03-14 1976-03-02 American Cyanamid Company Novel 3 or 5-aminopyrazolium salts and fungicidal use thereof

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